Survival after treatment with phenylacetate and benzoate for urea-cycle disorders
Survival after treatment with phenylacetate and benzoate for urea-cycle disorders
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DOI：
10.1056/nejmoa066596
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发表时间：
2007-05-31
影响因子：
158.5
通讯作者：
Hamosh, Ada
中科院分区：
文献类型：
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作者：
Enns, Gregory M.;Berry, Susan A.;Hamosh, Ada
背景：静脉注射苯乙酸钠和苯甲酸钠已被证明可以降低血浆铵水平，提高历史上致命的尿素循环酶缺陷患者的小队列生存率。方法：我们报告了一项为期25年、开放标签、非对照研究的结果，该研究使用苯乙酸钠和苯甲酸钠治疗299例尿循环障碍患者，其中有1181例急性高氨血症发作。结果：总生存率为84%（299例患者中有250例）。96%的患者在高氨血症发作后存活（1181次发作中的1132次）。30天以上的患者比新生儿更有可能在一次发作中存活（98%比73%，P < 0.001）。发生437次发作的12岁及以上患者（93例）比所有年轻患者更有可能存活（99%,P < 0.001）。入院时处于昏迷状态的病人有81%存活了下来。年龄小于30天且峰值氨浓度高于1000微mol / l（1804微克/分升）的患者在高氨血症发作中存活的可能性最小（38%,P < 0.001）。56名新生儿在60%的发作期间使用了透析，80名30天或以上的患者在7%的发作期间使用了透析。结论：及时识别尿素循环障碍，同时使用苯乙酸钠和苯甲酸钠治疗，并结合其他治疗，如静脉注射盐酸精氨酸和提供足够的卡路里以防止分解代谢，可有效降低血浆铵水平，并改善大多数患者的生存。血液透析也可能需要控制高氨血症，特别是对静脉注射苯乙酸钠和苯甲酸钠无反应的新生儿和老年患者。
BACKGROUND:The combination of intravenous sodium phenylacetate and sodium benzoate has been shown to lower plasma ammonium levels and improve survival in small cohorts of patients with historically lethal urea-cycle enzyme defects.METHODS:We report the results of a 25-year, open-label, uncontrolled study of sodium phenylacetate and sodium benzoate therapy (Ammonul, Ucyclyd Pharma) in 299 patients with urea-cycle disorders in whom there were 1181 episodes of acute hyperammonemia.RESULTS:Overall survival was 84% (250 of 299 patients). Ninety-six percent of the patients survived episodes of hyperammonemia (1132 of 1181 episodes). Patients over 30 days of age were more likely than neonates to survive an episode (98% vs. 73%, P < 0.001). Patients 12 or more years of age (93 patients), who had 437 episodes, were more likely than all younger patients to survive (99%, P < 0.001). Eighty-one percent of patients who were comatose at admission survived. Patients less than 30 days of age with a peak ammonium level above 1000 micromol per liter (1804 microg per deciliter) were least likely to survive a hyperammonemic episode (38%, P < 0.001). Dialysis was also used in 56 neonates during 60% of episodes and in 80 patients 30 days of age or older during 7% of episodes.CONCLUSIONS:Prompt recognition of a urea-cycle disorder and treatment with both sodium phenylacetate and sodium benzoate, in conjunction with other therapies, such as intravenous arginine hydrochloride and the provision of adequate calories to prevent catabolism, effectively lower plasma ammonium levels and result in survival in the majority of patients. Hemodialysis may also be needed to control hyperammonemia, especially in neonates and older patients who do not have a response to intravenous sodium phenylacetate and sodium benzoate.